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Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells

BACKGROUND: Variations of microRNA (miRNA) expression profile in hypoxic lung cancer cells have not been studied so far. Therefore, using miRNA microarray technology, this study aimed to study the miRNA expression profile and investigate the potential crucial miRNAs and their target genes in hypoxia...

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Autores principales: Geng, Ying, Deng, Lili, Su, Dongju, Xiao, Jinling, Ge, Dongjie, Bao, Yongxia, Jing, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966693/
https://www.ncbi.nlm.nih.gov/pubmed/27524914
http://dx.doi.org/10.2147/OTT.S103430
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author Geng, Ying
Deng, Lili
Su, Dongju
Xiao, Jinling
Ge, Dongjie
Bao, Yongxia
Jing, Hui
author_facet Geng, Ying
Deng, Lili
Su, Dongju
Xiao, Jinling
Ge, Dongjie
Bao, Yongxia
Jing, Hui
author_sort Geng, Ying
collection PubMed
description BACKGROUND: Variations of microRNA (miRNA) expression profile in hypoxic lung cancer cells have not been studied so far. Therefore, using miRNA microarray technology, this study aimed to study the miRNA expression profile and investigate the potential crucial miRNAs and their target genes in hypoxia-induced human lung adenocarcinoma cells. MATERIALS AND METHODS: Based on miRNA microarray, miRNA expression profiling of hypoxia-induced lung adenocarcinoma A549 cells was obtained. After identification of differentially expressed miRNAs (DE-miRNAs) in hypoxic cells, target genes of DE-miRNAs were predicted, and functional enrichment analysis of targets was conducted. Furthermore, the expression levels of DE-miRNAs and their target genes were validated by real-time quantitative polymerase chain reaction. In addition, using miRNA mimics, the effect of overexpressed DE-miRNAs on A549 cell behaviors (cell proliferation, cell cycle, and apoptosis) was evaluated. RESULTS: In total, 14 DE-miRNAs (nine upregulated miRNAs and five downregulated miRNAs) were identified in hypoxic cells, compared with normoxic cells. Target genes of both upregulated and downregulated miRNAs were enriched in the functions such as chromatin modification, and pathways such as Wnt signaling pathway and transforming growth factor (TGF)-β signaling pathway. The expression levels of several miRNAs and their target genes were confirmed, including hsa-miR-301b/FOXF2, hsa-miR-148b-3p/WNT10B, hsa-miR-769-5p/(SMAD2, ARID1A), and hsa-miR-622. Among them, hsa-miR-301b was verified to regulate FOXF2, and hsa-miR-769-5p was verified to modulate ARID1A. In addition, the overexpression of hsa-miR-301b and hsa-miR-769-5p significantly affected the cell cycle of A549 cells, but not cell proliferation and apoptosis. CONCLUSION: miRNA expression profile was changed in hypoxia-induced lung cancer cells. Those validated miRNAs and genes may play crucial roles in the response of lung cancer cells to hypoxia.
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spelling pubmed-49666932016-08-12 Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells Geng, Ying Deng, Lili Su, Dongju Xiao, Jinling Ge, Dongjie Bao, Yongxia Jing, Hui Onco Targets Ther Original Research BACKGROUND: Variations of microRNA (miRNA) expression profile in hypoxic lung cancer cells have not been studied so far. Therefore, using miRNA microarray technology, this study aimed to study the miRNA expression profile and investigate the potential crucial miRNAs and their target genes in hypoxia-induced human lung adenocarcinoma cells. MATERIALS AND METHODS: Based on miRNA microarray, miRNA expression profiling of hypoxia-induced lung adenocarcinoma A549 cells was obtained. After identification of differentially expressed miRNAs (DE-miRNAs) in hypoxic cells, target genes of DE-miRNAs were predicted, and functional enrichment analysis of targets was conducted. Furthermore, the expression levels of DE-miRNAs and their target genes were validated by real-time quantitative polymerase chain reaction. In addition, using miRNA mimics, the effect of overexpressed DE-miRNAs on A549 cell behaviors (cell proliferation, cell cycle, and apoptosis) was evaluated. RESULTS: In total, 14 DE-miRNAs (nine upregulated miRNAs and five downregulated miRNAs) were identified in hypoxic cells, compared with normoxic cells. Target genes of both upregulated and downregulated miRNAs were enriched in the functions such as chromatin modification, and pathways such as Wnt signaling pathway and transforming growth factor (TGF)-β signaling pathway. The expression levels of several miRNAs and their target genes were confirmed, including hsa-miR-301b/FOXF2, hsa-miR-148b-3p/WNT10B, hsa-miR-769-5p/(SMAD2, ARID1A), and hsa-miR-622. Among them, hsa-miR-301b was verified to regulate FOXF2, and hsa-miR-769-5p was verified to modulate ARID1A. In addition, the overexpression of hsa-miR-301b and hsa-miR-769-5p significantly affected the cell cycle of A549 cells, but not cell proliferation and apoptosis. CONCLUSION: miRNA expression profile was changed in hypoxia-induced lung cancer cells. Those validated miRNAs and genes may play crucial roles in the response of lung cancer cells to hypoxia. Dove Medical Press 2016-07-25 /pmc/articles/PMC4966693/ /pubmed/27524914 http://dx.doi.org/10.2147/OTT.S103430 Text en © 2016 Geng et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Geng, Ying
Deng, Lili
Su, Dongju
Xiao, Jinling
Ge, Dongjie
Bao, Yongxia
Jing, Hui
Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells
title Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells
title_full Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells
title_fullStr Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells
title_full_unstemmed Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells
title_short Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells
title_sort identification of crucial micrornas and genes in hypoxia-induced human lung adenocarcinoma cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966693/
https://www.ncbi.nlm.nih.gov/pubmed/27524914
http://dx.doi.org/10.2147/OTT.S103430
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